Baicalin’s Influence On Animal Behavior And Interferes With The Protein Expression Of Kir4.1in Rats Hippocampal After Lithium-pilocarpine Induced Status Epileptitus

Objective:(1) To explore the most effective dose of baicalin byobserving whether different doses of baicalin pretreatment altered the seizureactivity on the lithium–pilocarpine induced status epilepticus(Li-Pilo SE)model；(2) To study the underlying mechanisms of baicalin interferes bymeasuring the influence of kir4.1protein expression on the lithium–pilocarpine induced status epilepticus rats with the most effective dose ofbaicalin pretreatment. Materials and methods:1) Cleaning degree nomal maleSD rats,8-10weeks old, were used for the experiment and were randomlydivided into control group(n=5), epilepsy model group (n=12), baicalinpretreatment groups (100，200，400，800mg/kg, per group n=12). Epilepsymodel group were intraperitoneal injected with lithium chloride and pilocarpineto induced status epilepticus. baicalin pretreatment groups were injected withlithium chloride and pilocarpine respectively30minutes after giving baicalin(100,200,400,800mg/kg) by intraperitoneal injection, epilepsy model groupand control group at the same time given only normal saline by intraperitonealinjection, then, we observed seizures severity scale and the latent period of therats.((2) Cleaning degree nomal male SD rats,8-10weeks old, were used forthe experiment and were randomly divided into control group, epilepsy modelgroup, Baicalin (the most effective dose) pretrement group, the modelingapproach according to the first part.They were puted to death at1thday,3thdayafter SE induction,5rats in each subgroup. making specimens for Western-blot,the expression of kir4.1protein in were detected by the methed of Western-blotat1thday,3thday after SE induction in each group. Results:(1))Behavioralobservation results: compared with the epilepsy model group, different doses ofbaicalin pretrement groups prolonged the latent period reaching grade Ⅳ-Ⅴ according to the Racine’s scale,and the difference was statistically significant(P <0.05), the difference of different doses of baicalin pretreatment groups wasno significant difference (P>0.05); compared with model group, seizures Ⅳ-Ⅴgrade incidence were lower in different doses of baicalin (100,200,400,800mg/kg) pretreatment groups, and the difference was statistically significant(P <0.05), the difference of different doses of baicalin pretreatment groups wasno significant difference (P>0.05).(2) Western blot showed that the level ofkir4.1protein at1thday,3thday after SE induction in hippocampus was reducedin the model group compared with control group, difference of the mean opticaldensity ratio between the two groups was statistically significant (P <0.01).compared with model group, the mean optical density ratio of baicalin（200mg/kg）pretreatment group in at1thday,3thday after SE induction wassignificantly increasing, the difference between the two groups was statisticallysignificant (P <0.01).Conclusion:(1) In lithium–pilocarpine induced statusepilepticus model,different doses of baicalin pretreatment could significantlyprolong the latency(seizures grade Ⅳ-Ⅴ)and reduce seizures grade Ⅳ-Ⅴincidence, although the latency(seizures grade Ⅳ-Ⅴ) and seizures grade Ⅳ-Ⅴ incidence had no difference after different doses of baicalin pretreatment, itwas obvisious that the latency had significantly prolonging trend with baicalin200mg/kg pretreatment, and when the dose was increased to400mg/kg,800mg/kg, there was a decreasing trend, which was probably because of thesmall sample size, so there is no significant difference. Thus, we suggested thatthe best possible effective dose of baicalin is200mg/kg, which hadsignificant antiepileptic effect.(2)The expression of kir4.1protein wassignificantly reduced in lithium-pilocarpine-induced status epilepticus rats,giving baicalin pretreatment inhibited the decreasing trend of the expressionof kir4.1protein, and the expression of kir4.1protein significantly increased.Antiepileptic effect of baicalin on lithium-pilocarpine status epilepticus model may be the result of interaction of multiple targets, however, raising heexpression of kir4.1protein in rats hippocampus may be one of important rolein the antiepileptic mechanism.